Abstract

Middle East respiratory syndrome (MERS-COV), first identified in Saudi Arabia, was caused by a novel strain of coronavirus. Outbreaks were recorded from different regions of the world, especially South Korea and the Middle East, and were correlated with a 35% mortality rate. MERS-COV is a single-stranded, positive RNA virus that reaches the host by binding to the receptor of dipeptidyl-peptides. Because of the unavailability of the vaccine available for the protection from MERS-COV infection, the rapid case detection, isolation, infection prevention has been recommended to combat MERS-COV infection. So, vaccines for the treatment of MERS-COV infection need to be developed urgently. A possible antiviral mechanism for preventing MERS-CoV infection has been considered to be MERS-CoV vaccines that elicit unique T-cell responses. In the present study, we incorporated both molecular docking and immunoinformatic approach to introduce a multiepitope vaccine (MEP) against MERS-CoV by selecting 15 conserved epitopes from seven viral proteins such as three structural proteins (envelope, membrane, and nucleoprotein) and four non-structural proteins (ORF1a, ORF8, ORF3, ORF4a). The epitopes, which were examined for non-homologous to host and antigenicity, were selected on the basis of conservation between T-cell, B-cell, and IFN-γ epitopes. The selected epitopes were then connected to the adjuvant (β-defensin) at the N-terminal through an AAY linker to increase the immunogenic potential. Structural modelling and physiochemical characteristic were applied to the vaccine construct developed. Afterwards the structure has been successfully docked with antigenic receptor, Toll-like receptor 3 (TLR-3) and in-silico cloning ensures that its expression efficiency is legitimate. Nonetheless the MEP presented needs tests to verify its safety and immunogenic profile.

Highlights

  • MERS-COV was found in the Saudi Arabia kindgom as a highly pathogenic beta coronavirus in 2012, causing extreme acute respiratory diseases [1,2,3]

  • During the severe course of MERS-CoV infection, unique T-cell responses are evoked towards non-structural MER-CoV proteins, so the response tends towards structural MERS-CoV proteins during infection [65]

  • Few of the epitopes predicted in our study are the part of determined regions, predicted in the study of multiepitope vaccine (MEP) construction against MERS performed by Srivastava, S., et al, such as GDLLYLDLLNRLQAL and MDYVSLLN in nucleoprotein and ORF4a respectively [68]

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Summary

Introduction

MERS-COV was found in the Saudi Arabia kindgom as a highly pathogenic beta coronavirus in 2012, causing extreme acute respiratory diseases [1,2,3]. Present studies suggested that insectivorous bats (Neoromicia capensis and Vespertilio superans) are considered to be the source, dromedary camels and European hedgehog are natural host and source of human MERS-COV transmission [1, 4]. HDPP4 (Human dipeptidyl peptidase 4) was found to be MERS-COV receptor [5]. Membrane (M), lower interferon (IFN) level in affected people, and nucleoprotein (N) responsible for RNA binding takes place during ribonucleocapsid formation by MERS-COV due to this protein [8]. MERS-COV has infected about 2,100 people and has a fatality rate of about 35% [10, 11]. Most of the patients infected with MERS-COV had comorbidities like diabetes and considered to be more severe in patients with a weakened immune system [11]. As there is no therapeutic or vaccine available in market against MERS-COV

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